Moraxella (Branhamella) catarrhalis bacteria are Gram-negative diplococcal pathogens which are carried asymptomatically in the healthy human respiratory tract. However, in recent years, M. catarrhalis has been recognized as an important causative agent of otilis media. In addition, M. catarrhalis has been associated with sinusitis, conjunctivitis, and urogenital infections, as well as with a number of inflammatory diseases of the lower respiratory tract in children and adults, including pneumonia, chronic bronchitis, tracheitis, and emphysema (refs. 1 to 8). (Throughout this application, various references are cited in parentheses to describe more fully the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosures of these references are hereby incorporated by reference into the present disclosure). Occasionally, M. catarrhalis invades to cause septicaemia, arthritis, endocarditis, and meningitis (refs. 9 to 13).
M. catarrhalis colonizes the human upper respiratory tract and is an important cause of otitis media in infants and children as well as lower respiratory tract infections in adults with chronic obstructive pulmonary disease.
Otitis media is one of the most common illnesses of early childhood and approximately 80% of all children suffer at least one middle ear infection before the age of three (ref. 14). Chronic otitis media has been associated with auditory and speech impairment in children, and in some cases, has been associated with learning disabilities. Conventional treatments for otitis media include antibiotic administration and surgical procedures, including tonsillectomies, adenoidectomies, and tympanocentesis. In the United States, treatment costs for otitis media are estimated to be between one and two billion dollars per year.
In otitis media cases, M. catarrhalis is commonly co-isolated from middle ear fluid along with Streptococcus pneumoniae and non-typable Haemophilus influenzae, which are believed to be responsible for 50% and 30% of otitis media infections, respectively. M. catarrhalis is believed to be responsible for approximately 20% of otitis media infections (ref. 15). Epidemiological reports indicate that the number of cases of otitis media attributable to M. catarrhalis is increasing, along with the number of antibiotic-resistant isolates of M. catarrhalis. Thus, prior to 1970, no .beta.-lactamase-producing M. catarrhalis isolates had been reported, but since the mid-seventies, an increasing number of .beta.-lactamase-expressing isolates have been detected. Recent surveys suggest that up to 80 to 85% of clinical isolates produce .beta.-lactamase (ref. 16, 22, 23).
Iron-restriction is a general host defence mechanism against microbial pathogens. A number of bacterial species including Neisseria meningitidis (ref. 17, 24), N. gonorrhoeae (ref. 25) and M. catarrhalis (ref. 17), express outer membrane proteins which specifically bind human lactoferrin.
M. catarrhalis infection may lead to serious disease. It would be advantageous to provide a recombinant source of lactoferrin binding proteins as antigens in immunogenic preparations including vaccines, carriers for other antigens and immunogens and the generation of diagnostic reagents. The genes encoding lactoferrin binding proteins and fragments thereof are particularly desirable and useful in the specific identification and diagnosis of Moraxella and for immunization against disease caused by M. catarrhalis and for the generation of diagnostic reagents.